How Can We Identify Very High-Risk Heterozygous Familial Hypercholesterolemia?

Heterozygous familial hypercholesterolemia (HeFH) is a genetic disorder that elevates low-density lipoprotein cholesterol and increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). However, despite their atherogenic lipid profiles, the cardiovascular risk of HeFH varies in each individual. Their variety of phenotypic features suggests the need for better risk stratification to optimize their therapeutic management. The current review summarizes three potential approaches, including (1) definition of familial hypercholesterolemia (FH)-related risk scores, (2) genetic analysis, and (3) biomarkers. The International Atherosclerosis Society has recently proposed a definition of severe FH to identify very high-risk HeFH subjects according to their clinical characteristics. Furthermore, published studies have shown the association of FH-related genetic phenotypes with ASCVD, which indicates the genetic analysis’s potential to evaluate individual cardiovascular risks. Biomarkers reflecting disease activity have been considered to predict the formation of atherosclerosis and the occurrence of ASCVD in HeFH subjects. Incorporating these risk stratifications will be expected to allocate adequate intensity of lipid-lowering therapies in HeFH subjects, which ultimately improves cardiovascular outcomes.     

Transplantation of bone marrow stromal cell-derived Schwann cells promotes axonal regeneration and functional recovery after complete transection of adult rat spinal cord

The aim of this study was to evaluate whether transplantation of Schwann cells derived from bone marrow stromal cells (BMSC-SCs) promotes axonal regeneration and functional recovery in completely transected spinal cord in adult rats. Bone marrow stromal cells (BMSCs) were induced to differentiate into Schwann cells in vitro. A 4-mm segment of rat spinal cord was removed completely at the T7 level. An ultra-filtration membrane tube, filled with a mixture of Matrigel (MG) and BMSC-SCs (BMSC-SC group) or Matrigel alone (MG group), was grafted into the gap. In the BMSC-SC group, the number of neurofilament- and tyrosine hydroxylase-immunoreactive nerve fibers was significantly higher compared to the MG group, although 5-hydroxytryptamine- or calcitonin gene-related peptide-immunoreactive fibers were rarely detectable in both groups. In the BMSC-SC group, significant recovery of the hindlimb function was recognized, which was abolished by retransection of the graft 6 weeks after transplantation. These results demonstrate that transplantation of BMSC-SCs promotes axonal regeneration of lesioned spinal cord, resulting in recovery of hindlimb function in rats. Transplantation of BMSC-SCs is a potentially useful treatment for spinal cord injury.     

Solitary fibrous benign mesothelioma of the peritoneum: Report of a case

A 66-year-old Japanese man who had undergone a subtotal gastrectomy for gastric cancer 1 year earlier, and was asymptomatic, underwent a computed tomography scan during a detailed follow-up examination, which revealed a pancreatic mass. Abdominal ultrasonography showed a solid tumor containing a cystic lesion, and abdominal magnetic resonance demonstrated a tumor with low intensity on T1-weighted images and high intensity on T2-weighted images. Although an abdominal angiography added no new information to help in establishing a preoperative diagnosis, it showed an avascular mass. An endoscopic retrograde pancreatograhy showed compression and deviation of the body part of the pancreatic duct, and dilatation of its caudal part. At laparotomy, an elastic soft tumor was found to originate from the peritoneum of the omental bursa in front of the pancreas. The tumor was encapsulated and solid. The solid lesion consisted of spindle-shaped cells, but no atypical cells were observed. The histological findings were diagnostic of a benign solitary fibrous mesothelioma, which is extremely rare. The patient is currently well and disease-free more than 5 years after this operation.     

Antegrade selective cerebral perfusion with mild hypothermic systemic circulatory arrest during thoracic aortic surgery

Objective Antegrade selective cerebral perfusion (ASCP) and retrograde cerebral perfusion (RCP) have proven to be reliable methods of brain protection during aortic surgery. These techniques are usually accompanied by systemic circulatory arrest with moderate hypothermia (24–28°C) or deep hypothermia (18–24°C). However, hypothermia can lead to various problems. The present study therefore reports results for thoracic aorta replacement using ASCP with mild hypothermic systemic arrest (28–32°C).

Design Between 1995 and 2003, 68 consecutive patients underwent repair of the ascending aorta and/or aortic arch. Mild hypothermic ASCP was utilized in 31 cases, moderate hypothermic ASCP in 20, and deep hypothermic RCP in 17. Various parameters were compared between the mild hypothermic ASCP, moderate hypothermic ASCP, and RCP.

Results Hospital mortality was 10.3%, with no significant differences observed between any groups. Permanent neurological dysfunction was 8.8%, and no significant differences were observed between any groups. Mild hypothermic ASCP displayed significantly decreased transfusion volume, intubation time, and ICU stay.

Conclusions Use of ASCP with mild hypothermic systemic circulatory arrest during aortic surgery resulted in acceptable hospital mortality and neurological outcomes. ASCP with mild hypothermic arrest allows decreased transfusion volume and reduced duration of intubation and ICU stay.     

Anatomic renal artery branch microdissection to facilitate zero-ischemia partial nephrectomy

Background

Robot-assisted and laparoscopic partial nephrectomies (PNs) for medial tumors are technically challenging even with the hilum clamped and, until now, were impossible to perform with the hilum unclamped.

Objective

Evaluate whether targeted vascular microdissection (VMD) of renal artery branches allows zero-ischemia PN to be performed even for challenging medial tumors.

Design, setting, and participants

A prospective cohort evaluation of 44 patients with renal masses who underwent robot-assisted or laparoscopic zero-ischemia PN either with anatomic VMD (group 1; n = 22) or without anatomic VMD (group 2; n = 22) performed by a single surgeon from April 2010 to January 2011.

Intervention

Zero-ischemia PN with VMD incorporates four maneuvers: (1) preoperative computed tomographic reconstruction of renal arterial branch anatomy, (2) anatomic dissection of targeted, tumor-specific tertiary or higher-order renal arterial branches, (3) neurosurgical aneurysm microsurgical bulldog clamp(s) for superselective tumor devascularization, and (4) transient, controlled reduction of blood pressure, if necessary.

Measurements

Baseline, perioperative, and postoperative data were collected prospectively.

Results and limitations

Group 1 tumors were larger (4.3 vs 2.6 cm; p = 0.011), were more often hilar (41% vs 9%; p = 0.09), were medial (59% and 23%; p = 0.017), were closer to the hilum (1.46 vs 3.26 cm; p = 0.0002), and had a lower C index score (2.1 vs 3.9; p = 0.004) and higher RENAL nephrometry scores (7.7 vs 6.2; p = 0.013). Despite greater complexity, no group 1 tumor required hilar clamping, and perioperative outcomes were similar to those of group 2: operating room time (4.7 and 4.1 h), median blood loss (200 and 100 ml), surgical margins for cancer (all negative), major complications (0% and 9%), and minor complications (18% and 14%). The median serum creatinine level was similar 2 mo postoperatively (1.2 and 1.3 mg/dl). The study was limited by the relatively small sample size.

Conclusions

Anatomic targeted dissection and superselective control of tumor-specific renal arterial branches facilitate zero-ischemia PN. Even challenging medial and hilar tumors can be excised without hilar clamping. Global surgical renal ischemia has been eliminated for most patients undergoing PN at our institution.     

Three-dimensional reconstruction of renovascular-tumor anatomy to facilitate zero-ischemia partial nephrectomy

Zero-ischemia robotic and laparoscopic partial nephrectomy, a novel concept, eliminates ischemia to the tumor-free normal kidney. Anatomic microdissection of tertiary/higher-order tumor-specific arteries is performed to selectively devascularize only the tumor, maintaining normal perfusion of the remaining kidney. A thorough understanding of renovascular tumor anatomy is essential. Based on 0.5-mm-slice thickness computed tomography scans, we developed a novel three-dimensional (3D) reconstruction technique that fuses three key anatomic aspects: surface-rendered tumor, semitransparent kidney, and extra- and intrarenal arterial anatomy. Four central completely intrarenal hilar masses underwent 3D reconstruction for surgical navigation during zero-ischemia partial nephrectomy. Negative surgical margins were obtained in all four cases, with no intraoperative complications or transfusions. For these challenging laparoscopically invisible masses, 3D image navigation precisely identified tumor-specific arterial branches, thus facilitating zero-ischemia partial nephrectomy without hilar cross clamping.     

A case of acute renal failure after exercise with renal hypouricemia demonstrated compound heterozygous mutations of uric acid transporter 1

Familial renal hypouricemia is a hereditary disease characterized by extraordinary high renal uric acid (UA) clearance and is associated with acute renal failure (ARF). A 17-year-old Japanese male developed ARF after anerobic exercise. Renal function improved completely after approximately 2 weeks of hydration treatment. After remission, hypouricemia became evident (1.0 mg/dL) from the initial level of UA (4.8 mg/dL) and fractional excretion of uric acid (FEUA) was >50%. His parents showed normal levels of UA and FEUA. Polymerase chain reaction of a urate anion exchanger known to regulate UA level [SLC22A12 gene: UA transporter 1 (URAT1)] demonstrated compound heterozygous mutations (Q297X and R90H). Thus, we describe a Japanese male with hypouricemia complicated by anerobic exercise-induced ARF, with definite demonstration of a genetic abnormality in the responsible gene, URAT1.     

Intraluminal lavage to remove exfoliated tumor cells after colorectal endoscopic submucosal dissection

Background

Endoscopic submucosal dissection (ESD) involves dissection of tumors and manipulation of them in an exposed condition for prolonged periods. A large number of tumor cells are exfoliated into the intestinal lumen after colorectal ESD. The aim of this study was to determine whether lavage volume has an influence on tumor cell clearance after colorectal ESD.

Methods

Twenty patients who underwent colorectal ESD at our hospital between July 2013 and December 2014 were studied. Cytological examination of intraluminal lavage samples associated incremental increases in lavage volume was collected. This prospective study was approved by the ethics committee of our hospital.

Results

No patients had exfoliated tumor cells in their samples before ESD. Four patients (20 %) had exfoliated tumor cells in their samples after lavage with 500 ml, while one patient (5 %) had exfoliated tumor cells after lavage with 1000 or 1500 ml.

Conclusion

Tumor cells are exfoliated into the intestinal lumen by tumor manipulation during colorectal ESD. There seems to be a risk for implantation after ESD, as well as rectal surgery. Sufficient intraluminal lavage of more than 1000 ml may be desirable to remove exfoliated tumor cells after colorectal ESD.

     

Multiple antiplatelet therapy contributes to the reversible high signal spots on diffusion-weighted imaging in elective coiling of unruptured cerebral aneurysm

Introduction

Our aim was to systematically investigate radiographic characteristics and outcome of diffusion-weighted imaging (DWI) changes in the elective coiling of unruptured cerebral aneurysm with analyzing the correlation of antiplatelet therapy (APT).

Methods

In a total of 34 consecutive patients with unruptured cerebral aneurysms initially treated by coiling without stent assist, 26 (76.5 %) had DWI changes with 91 high signal spots within 24–48 h after the procedure. We recorded DWI parameters (location, volume, mean, and minimum values of the apparent diffusion coefficient: expressed as ADC_AVE and ADC_MIN) for each lesion, and evaluated its radiographic outcome on conventional MRI at follow-up (interval, 58.4?±?37.2 days) in the modes of APT.

Results

All patients with DWI high spots had no clinical symptoms. There was a strong correlation between ADC_AVE and ADC_MIN (r?=?0.82, p?<?0.0001). The mean ADC_AVE and rADC_AVE were 0.74?±?0.14?×?10^?3?mm²/s and 87?±?10 %. DWI high spots were small with a mean volume of 0.13?±?0.12 cm³, ranging from 0.04 to 0.86 cm³. A negative correlation was observed between the volume and values of ADC_AVE (r?=??0.48, p?<?0.0001). The DWI volume was significantly larger in single APT than in multiple (0.15?±?0.14 versus 0.10?±?0.07 cm³, p?=?0.0091). The permanent signal change was more observed in single APT than in multiple (24.5 % versus 5.2 %, p?=?0.02).

Conclusion

DWI high spots after elective coiling were small without significant decrease of ADC, and do not correspond to brain infarction. Periprocedural use of multiple antiplatelet agents is expected to reduce the volume of thromboembolism and permanent tissue damages.